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dc.contributor.authorAdamian, Larisa
dc.contributor.authorNaveed, Hammad
dc.contributor.authorLiang, Jie
dc.date.accessioned2011-05-26T02:37:07Z
dc.date.available2011-05-26T02:37:07Z
dc.date.issued2011-04
dc.identifier.bibliographicCitationAdamian, L., Naveed, H., & Liang, J. 2011. Lipid-Binding Surfaces of Membrane Proteins: Evidence From Evolutionary and Structural Analysis. Biochimica Et Biophysica Acta-Biomembranes, 1808(4): 1092-1102. DOI: 10.1016/j.bbamem.2010.12.008en
dc.identifier.issn0006-3002
dc.identifier.otherDOI: 10.1016/j.bbamem.2010.12.008
dc.identifier.urihttp://hdl.handle.net/10027/7670
dc.descriptionNOTICE: this is the author’s version of a work that was accepted for publication in Biochimica et Biophysica Acta. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochimica et Biophysica Acta, [VOL 1808, ISSUE 4, (April 2011)] DOI: 10.1016/j.bbamem.2010.12.008. The original publication is available at www.elsevier.com.en
dc.description.abstractMembrane proteins function in the diverse environment of the lipid bilayer. Experimental evidence suggests that some lipid molecules bind tightly to specific sites on the membrane protein surface. These lipid molecules often act as co-factors and play important functional roles. In this study, we have assessed the evolutionary selection pressure experienced at lipid-binding sites in a set of alpha-helical and beta-barrel membrane proteins using posterior probability analysis of the ratio of synonymous vs. nonsynonymous substitutions (omega-ratio). We have also carried out a geometric analysis of the membrane protein structures to identify residues in close contact with co-crystallized lipids. We found that residues forming cholesterol-binding sites in both beta(2)-adrenergic receptor and Na+-K+-ATPase exhibit strong conservation, which can be characterized by an expanded cholesterol consensus motif for GPCRs. Our results suggest the functional importance of aromatic stacking interactions and interhelical hydrogen bonds in facilitating protein-cholesterol interactions, which is now reflected in the expanded motif. We also find that residues forming the cardiolipin-binding site in formate dehydrogenase-N gamma-subunit and the phosphatidylglycerol binding site in KcsA are under strong purifying selection pressure. Although the lipopolysaccharide (LPS)-binding site in ferric hydroxamate uptake receptor (FhuA) is only weakly conserved, we show using a statistical mechanical model that LPS binds to the least stable FhuA beta-strand and protects it from the bulk lipid. Our results suggest that specific lipid binding may be a general mechanism employed by beta-barrel membrane proteins to stabilize weakly stable regions. Overall, we find that the residues forming specific lipid binding sites on the surfaces of membrane proteins often experience strong purifying selection pressure.en
dc.language.isoen_USen
dc.publisherElsevieren
dc.subjectLipid bindingen
dc.subjectcholesterol binding motifen
dc.subjectlipopolysaccharideen
dc.titleLipid-Binding Surfaces of Membrane Proteins: Evidence From Evolutionary and Structural Analysisen
dc.typeArticleen


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